Parts of the Puzzle

1. Parts of the Puzzle

2. IBR at work

3. the role of antibiotics in treating diseases caused by different bugs … focus on respiratory disease • Shipping fever / BRD … set up by lack of immune protection stress, commingling, & timing • Virus destroys cells that protect the lung … • Bacteria move from their hang out to lung • Lungs cells provide lots of food with very little defense

6. Disease sequence of events: • Susceptible animal exposed. • Incubation is the period (time) from the first replication of the disease causing biological agent until sufficient compromise of the target organ(s) occurs causing loss of function of the target organ(s). • Primary viral BRD this averages 3 days. • Secondary bacterial BRD averages 3 to 5 days behind the initial viral infection.

7. Disease sequence of events: • Inflammation occurs in stages. • Early, the body diverts white blood cells and blood in to the affected area typically causing swelling of tissue, both cells and spaces between cells. • As the inflammation continues, loss of function of the affected tissue occurs. • Late stage of inflammation is involved in the body trying to clean up, remove, or repair / reconstruct the damaged tissue. • The late stage of inflammation is the first stage of recovery. … begins 7 to 10 days … last for weeks

10. how the antibiotics work • Antibiotic – mold, 1928 • Protect molds from bacteria • No effect on viruses or normal body cells • Two types -static (slows) & cidal (kills) • Four mechanisms • Cripples cell wall • Interferes with protein synthesis • Confuses metabolic processes • Blocks DNA / RNA synthesis • Different bacteria … require different mechanisms to stop them …

11. antibiotic resistance mechanisms • Decrease Cell Wall Uptake / Perm • Aminoglycosides • Efflux • Macrolides, fluoroquinolones, tetracyclines • Enzymes Induced • Aminoglycosides, florfenicol, beta-lactams • Altered Target Binding Sites • Ribosome …macrolides, lincosamides • Wall Protein … beta-lactams, glycopeptides • DNA … fluoroquinolones • Gene Resistance • Plasmids … b-lact, tetra, macro, linco, fluro, sulfa • Transposons … beta-lactams, glycopeptides • Chromosome … beta-lactams, fluoroquinolones

15. PK / PD Relationships

16. Antibiotic Movement

19. FDA CVM Cephalosporin Update

20. Cephalosporin Extralabel Prohibition, April 5, 2012 • Response to public’s concern for antibiotic resistance development associated with agriculture use. • Applies to cattle, swine, chickens, turkeys • Prohibits unapproved dose levels, frequencies, durations or route of administration • Prohibits use in species in which it is not approved (does not apply to minor food species) • Prohibits use for prevention purposes

21. Griffin’s “prevention” vs. “control” use of antibiotic definition • The use of antibiotic (s) for "prevention” apply to situations in which the “animal or group of animals" might be/would be exposedto a disease causing bacterium/bacteria.   • Whereas the use of antibiotic (s) for "control" would apply to situations in which the “animal or group of animals" have been exposed AND the disease process caused by the bacterium/bacteria as begun in some or all of the group of animals as judged by an understanding of the disease process&/or signs (ex: depression, respiratory aberration, anorexia, etc.) have been observed in animals within the group.  

22. Guidance 209 “The judicious use of medically important antimicrobial drugs in food producing animals”, April 11 • Focus is not to ban, but on assuring drugs are used judiciously … use is a driver of resistance • “Medically Important Drugs”: GFI # 152 … penicillins, tetracyclines, aminoglycosides, macrolides, streptogramins and lincosamides … Not affected: bambermycin, bacitracin, ionophores • Phase out none therapeutic (growth promotion) use and phase in veterinary oversight for prevention, control and treatment

23. Draft Guidance 213 … “Road Map” of how to attain guidance 209, including a timeline, April 11, 2012 • GFI # 152: relative importance to medical community and the duration of use • Remove growth promotion from all antibiotics • Prevention use must be targeted at defined at-risk population (timing), a defined dosing duration & effective dosing levels • Implementation three year target for phasing in changes … Implement revised VFD requirements

24. Veterinary Feed Directive (VFD) … target the movement of OTC to Rx or VFD • VFD requirements will be changed … to become less onerous on veterinarians & to allow access to underserved livestock producers • Redefine: VFD form, VFD transmission, VFD record requirements & VFD VCPR requirement • Category 1 not withdrawal, Category 2 those with a withdrawal • Broaden(more flexible) animal identification requirement, number of animal, amount of feed, & expiration of VFD (up to six months) • VCPR (current 21 CFR 530) ... to … “veterinarian may only issue a VFD for use in animals under their supervision or oversight in the course of their professional practice, and in accordance with all applicable veterinary licensing and practice requirements”

25. What Those of Us Who Are Not Pharmacologist Need To Know About Selection & Use of Antibiotics The objective will be to help better understand: 1) how viruses and bacteria cause different diseases 2) how the antibiotics they use work 3) antibiotics role in treating diseases caused by different bugs 4) antibiotic classes … and what makes them different 5) why an antibiotic seems to work on some cattle & not others 6) how the other things we give sick cattle can influence an antibiotic's effectiveness 7) how to select a proper antibiotic for different diseases 8) how to know when to switch 9) which antibiotic would make a better choice when you need to switch if an animal doesn't respond 10) when to quit http://gpvec.unl.edu

27. why an antibiotic may seem to work on some sets of cattle and not others Source, Source, & Source • BIGGEST FACTOR … TIMING!!! • How much of a head start ??? • Animal’s ability to help fight back • Differences in bugs … • Diagnosis ???

28. Select appropriate high quality products • Most commonly, BRD has a head start in high-stressed young commingled cattle.

29. Prevention … is key Treatment salvages only part of the loss Immune preparation Treatment timing

30. Vaccine Titers

31. Dealing With Disease Don’t let your thermometer do your thinking! Appetite & Depression

32. Finding Sick Cattle … • Number one rule: ...Have plenty of timeearly every morning........If the temperature is going to be over 70-80 F that day ...... Be finished by 10AM • RELOOK AT CATTLE OFTEN

34. how the other things we give sick cattle can influence an antibiotic's effectiveness • The stress caused by some products does more damage than their benefit • Injection site irritation ??? • Restraint for IV injection … IV-ing ability • Product interferes with antibiotic • Sulfa’s and folic acid (a “B” vitamin)

35. “May Help … What It Don’t Hurt”

36. how to select a proper antibiotic for different diseases … will focus on BRD • Pneumonia … Ab penetration not as much of a problem early as late • Bugs that live in cells … need Ab that crosses cell walls • Animal’s that are over whelmed & can’t help the drug by fighting back … • cidal Ab may be better than static Ab • Can’t defend the use of Pen G (especially LA Pen) & Sulfa in BRD Rx programs • CAUTION – Generics …& AVOID Bathtub mixes • Neomycin & Gentamicin … violate BQA & reason

37. how to know when to switch • 1st … and very important … assess the “stress” effect of the Ab • gut fill, soreness, tissue temp, etc • don’t switch because of stress effect • Monitor animal NOT temp!!! • Don’t let the thermometer do your thinking • Use temp to confirm your visual assessment • Give the Ab 48 hours … @ MIC 90

38. which antibiotic would make a better choice when you need to switch … poor response • Re-check the diagnosis … • & evaluate the treatment extras being used • Use previous lab work … • animals that die may be the most valuable • If the infection is winning … get meaner • Cidal Ab KILL bugs … good selection • Ab that penetrate … good selection • Ab that minimizes stress effect … may be good • Have faith in the treatment plan … stick to it !

39. when to quit • Consider two things … 1) How long ago did the “stress” start ??? • Auction market … days received + 3 days 2) How long have you been treating animal? • If 1 is over 21days & 2 is over 7days … QUIT • If 2 is greater than 10 … QUIT

40. Letting go • Giving up on a sick animal that has failed to recover is one of the toughest things we ask our treatment crew to do. • Medications given to sick cattle that repeatedly fail to respond are extremely expensive. • Recognizing when it is time to stop therapy is tough, but simple rules for when to stop must be developed and enforced.

41. Letting go • Total cost of therapy may be a good guideline, but should be included with decisions based on the number of therapy days. • Management should evaluate continue therapy on all sick cattle that fail to respond with in seven days.

42. why an antibiotic may seem to work on some sets of cattle and not others Source … Immune prep history Source … Nutritional history Source … Stress & Commingling BIGGEST FACTOR … TIMING!!! How much of a head start ??? • Animal’s ability to help fight back • Differences in bugs … Diagnosis???

43. Prevention … is key Treatment salvages only part of the loss Immune preparation Treatment timing

44. Dealing With Disease Don’t let your thermometer do your thinking! Appetite & Depression

46. Finding Sick Cattle … • Hit the bulls eye with … DART • Depression • Appetite • Respiration • Temperature & never let the thermometer do your thinking!

47. Finding Sick Cattle … • Number one rule: ...Have plenty of timeearly every morning ....If the temperature is going to be over 80 F that day ...... Be finished by 10AM • RELOOK AT CATTLE OFTEN

48. how to select a proper antibiotic for different diseases … will focus on BRD • Pneumonia … Ab penetration not as much of a problem early as late • Bugs that live in cells … need Ab that crosses cell walls • Animal’s that are over whelmed & can’t help the drug by fighting back … • cidal Ab may be better than static Ab • Can’t defend the use of Pen G (especially LA Pen) & Sulfa in BRD Rx programs • CAUTION – Generics …& AVOID Bathtub mixes • Neomycin & Gentamicin … violate BQA & reason

49. how to know when to switch • 1st … and very important … assess the “stress” effect of the Ab • gut fill, soreness, tissue temp, etc. • don’t switch because of stress effect • Monitor animal NOT temp!!! • Don’t let the thermometer do your thinking • Use temp to confirm your visual assessment • Give the Ab 48 hours … @ MIC 90

50. which antibiotic would make a better choice when you need to switch … poor response • Re-check the diagnosis … • & evaluate the treatment extras being used • Use previous lab work … • animals that die may be the most valuable • If the infection is winning … get meaner • Cidal Ab KILL bugs … good selection • Ab that penetrate … good selection • Ab that minimizes stress effect … may be good • Have faith in the treatment plan … stick to it !